HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Evidence of environmental transfer of tebuconazole to the eggs in the house sparrow (Passer domesticus): An experimental study
No full textInternational audienceTriazole compounds are among the most widely used fungicides in agroecosystems to protect crops from potential fungal diseases. Many farmland birds spend a significant part of their life cycle in agroecosystems, which may chronically expose them to pesticides. We experimentally tested whether exposure to environmental concentrations of tebuconazole could induce a contamination of the eggs by tebuconazole in an agroecosystem sentinel species, the house sparrow (Passer domesticus). Wild-caught adult sparrows were maintained in captivity and exposed (exposed group) or not (control group) for seven months to tebuconazole through drinking water. Eggs were opportunistically collected for the determination of tebuconazole concentration by Liquid Chromatography coupled to tandem Mass Spectrometry in eggs. We found that eggs from exposed parents all contained tebuconazole with a mean concentration of 1.52 ng g−1 dry weight. In eggs from control parents, the tebuconazole concentration was below the limit of quantification (0.23 ng g−1 dry weight) for 11 out of 13 eggs. Thus, our study demonstrates for the first time that environmental exposure of female bi
ERRα coordinates actin and focal adhesion dynamics
No full textInternational audienceCell migration depends on the dynamic organisation of the actin cytoskeleton and assembly and disassembly of focal adhesions (FAs). However, the precise mechanisms coordinating these processes remain poorly understood. We previously identified the oestrogen-related receptor α (ERRα) as a major regulator of cell migration. Here, we show that loss of ERRα leads to abnormal accumulation of actin filaments that is associated with an increased level of inactive form of the actin-depolymerising factor cofilin. We further show that ERRα depletion decreases cell adhesion and results in defective FA formation and turnover. Interestingly, specific inhibition of the RhoA-ROCK-LIMK-cofilin pathway rescues the actin polymerisation defects resulting from ERRα silencing, but not cell adhesion. Instead, we found that MAP4K4 is a direct target of ERRα and down-regulation of its activity rescues cell adhesion and FA formation in the ERRα-depleted cells. Altogether, our results highlight a crucial role of ERRα in coordinating the dynamic of actin network and FAs through the independent regulation of the RhoA and MAP4K4 pathways
Prenatal exposure to organophosphate pesticides and autism spectrum disorders in 11-year-old children in the French PELAGIE cohort
No full textInternational audienceBackground: Organophosphate (OP) pesticides act by inhibiting acetylcholinesterase activity at synaptic junctions and have already been linked with deleterious effects on neurodevelopment, including autism spectrum disorders (ASD).Objectives: To investigate the association of prenatal exposure to OP pesticides with traits related to ASD in 11-year-old children.Methods: The "Childhood Autism Spectrum Test" (CAST) parent questionnaire was used to screen for autistic traits in 792 children from the French PELAGIE cohort. Prenatal maternal urine samples were collected 80%), terbufos and its metabolites least often (<10%). No association with ASD was found for DAP, terbufos or its metabolites. Incidence rate ratios (IRRs) increased with maternal urinary diazinon concentrations, from 1.11 (95% CI: 0.87-1.42) to 1.17 (95% CI: 0.94-1.46). Higher CAST scores were statistically significantly associated with the maternal urine samples in which chlorpyrifos or two of its metabolites (chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol) were detected. The IRR for exposure to chlorpyrifos or chlorpyrifos-oxon was 1.27 (95%CI: 1.05-1.52) among all children, and 1.39 (95%CI: 1.07-1.82) among boys.Conclusion: These findings suggest an increase in autistic traits among 11-year-old children in association with prenatal maternal exposure to chlorpyrifos and possibly diazinon. These associations were previously suspected in the literature, in particular for chlorpyrifos. Further work establishing the causal mechanisms behind these risk association is needed
Acute ozone exposure impairs detection of floral odor, learning, and memory of honey bees, through olfactory generalization
No full textInternational audienceAir pollution stemming from human activities affects the environment in which plant and animal species live and interact. Similar to primary air pollutants which are emitted, secondary air pollutants, such as tropospheric ozone (O3) formed from nitrogen oxides, are also harmful to human health and plant physiology. Yet, few reports studied the effects of O3 on pollinators' physiology, despite that this pollutant, with its high oxidative potential, likely affects pollinators behaviors, especially the perception of signals they rely on to navigate their environment. Volatile Organic Compounds (VOCs) released by plants are used as signals by different animals. For pollination services, VOCs attract different insects to the flowers and strengthen these interactions. Here, we used the honey bee Apis mellifera as a model to characterize the effects of acute exposure to different realistic mixing ratios of O3 (80-, 120-, and 200-ppb) on two crucial aspects: first, how exposed honey bees detect VOCs; and second, how O3 affects these pollinators' learning and memory processes. With electroantennogram (EAG) recordings, we showed that increasing O3 mixing ratios had a biphasic effect: an initial 25% decrease of the antennal activity when bees were tested directly after exposure (O3 direct effect), followed by a 25% increase in activity and response when bees were allowed a two-hour rest after exposure (O3 delayed effect). In parallel, during olfactory conditioning, increasing O3 mixing ratios in both exposure protocols scarcely affected olfactory learning, followed by a decrease in recall of learned odors and an increase of response to new odors, leading to a higher generalization rate (i.e., discrimination impairment). These results suggest a link between O3-related oxidative stress and olfactory coding disturbance in the honey bee brain. If ozone affects the pollinators' olfaction, foraging behaviors may be modified, in addition with a possible long-term harmful effect on pollination services
Cortical organoids to model microcephaly
No full textInternational audienceHow the brain develops and achieves its final size is a fascinating issue that questions cortical evolution across species and man’s place in the animal kingdom. Although animal models have so far been highly valuable in understanding the key steps of cortical development, many human specificities call for appropriate models. In particular, microcephaly, a neurodevelopmental disorder that is characterized by a smaller head circumference has been challenging to model in mice, which often do not fully recapitulate the human phenotype. The relatively recent development of brain organoid technology from induced pluripotent stem cells (iPSCs) now makes it possible to model human microcephaly, both due to genetic and environmental origins, and to generate developing cortical tissue from the patients themselves. These 3D tissues rely on iPSCs differentiation into cortical progenitors that self-organize into neuroepithelial rosettes mimicking the earliest stages of human neurogenesis in vitro. Over the last ten years, numerous protocols have been developed to control the identity of the induced brain areas, the reproducibility of the experiments and the longevity of the cultures, allowing analysis of the later stages. In this review, we describe the different approaches that instruct human iPSCs to form cortical organoids, summarize the different microcephalic conditions that have so far been modeled by organoids, and discuss the relevance of this model to decipher the cellular and molecular mechanisms of primary and secondary microcephalie
TRPM7 Modulates Human Pancreatic Stellate Cell Activation.
No full textInternational audiencePancreatic diseases, such as pancreatitis or pancreatic ductal adenocarcinoma, are characterized by the presence of activated pancreatic stellate cells (PSCs). These cells represent key actors in the tumor stroma, as they actively participate in disease development and progression: reprograming these PSCs into a quiescent phenotype has even been proposed as a promising strategy for restoring the hallmarks of a healthy pancreas. Since TRPM7 channels have been shown to regulate hepatic stellate cells proliferation and survival, we aimed to study the role of these magnesium channels in PSC activation and proliferation. PS-1 cells (isolated from a healthy pancreas) were used as a model of healthy PSCs: quiescence or activation were induced using all-trans retinoic acid or conditioned media of pancreatic cancer cells, respectively. The role of TRPM7 was studied by RNA silencing or by pharmacological inhibition. TRPM7 expression was found to be correlated with the activation status of PS-1 cells. TRPM7 expression was able to regulate proliferation through modulation of cell cycle regulators and most importantly p53, via the PI3K/Akt pathway, in a magnesium-dependent manner. Finally, the analysis of TCGA database showed the overexpression of TRPM7 in cancer-associated fibroblasts. Taken together, we provide strong evidences that TRPM7 can be considered as a marker of activated PSCs
Validation of a Parent-Reported Physical Activity Questionnaire by Accelerometry in European Children Aged from 6 to 12 Years Old
No full textInternational audienceValidated physical activity (PA) questionnaires are crucial for collecting information in large epidemiological studies during childhood. Thus, this study analyzed the validity of a parent-reported PA questionnaire based on the Children’s Leisure Activities Study Survey by accelerometry in European children aged from 6 to 12 years old. We used data from 230 children of the Human Early-Life Exposome and Infancia y Medio Ambiente projects. Mean differences between moderate-to-vigorous PA (MVPA) reported by the questionnaire and the accelerometer were calculated (min/day), and its associated factors were explored by multiple robust linear regression. The agreement between methods was examined using a Bland–Altman plot. The concurrent validity of assessing MVPA was analyzed by cohort-adjusted Spearman’s partial correlations. ROC curve analysis was also used to explore the questionnaire’s capability to identify active children based on the World Health Organization guidelines. A moderate correlation was found between parent-reported and accelerometer MVPA (rho = 0.41, p < 0.001). The child’s sex (girl) was statistically associated with the mean MVPA difference between methods. However, this questionnaire accurately identified physically active children (area under the curve = 83.8% and 82.7% for boys and girls, cut-points = 68.6 and 45.4 min/day in MVPA, respectively). Consequently, this questionnaire is suitable for classifying active children in order to monitor public health interventions regarding PA
Exposition de la population au bruit émis par les éoliennes en France métropolitaine
No full textContexte - Les lignes directrices de l'OMS relatives au bruit environnemental soulignent que les preuves concernant les effets sur la santé du bruit émis par les éoliennes sont soit inexistantes soit de faible qualité. Dans ce contexte, une étude de faisabilité a été conduite en France en 2017. Objectif - L'objectif était de proposer une méthodologie de calcul du bruit éolien pour déterminer le nombre de riverains exposés à différents niveaux de bruit audibles d'éoliennes et estimer ainsi les enjeux en termes de santé publique si des effets sur la santé venaient à être démontrés. Matériel et méthodes - Le choix du modèle de prévision du bruit Harmonoise a été validé en comparant des prévisions issues de ce modèle avec des mesures réalisées au cours d'une campagne sur un parc éolien. Les niveaux d'exposition déterminés à partir de ce modèle ont ensuite été croisés avec le nombre de personnes habitant à proximité des parcs éoliens. Le nombre de personnes exposées pour des conditions de propagation typiques de périodes diurne et nocturne a ainsi été déterminé à l'échelle de la métropole, et de chaque région française. Résultats - Comparativement à d'autres sources de bruit environnemental (les transports notamment), l'exposition au bruit des éoliennes est très modérée, avec plus de 80% de la population exposée qui l'est à des niveaux inférieurs à 40 dBA. Le nombre total de personnes exposées à plus de 30 dBA est d'environ 686 000 personnes pour des conditions de propagation diurne, et 722 000 personnes pour celles nocturnes, soit 1% de la population française métropolitaine en 2017. Conclusion - Ces résultats constituent la première évaluation de l'exposition des populations au bruit produit par les éoliennes en France métropolitaine
In silico prediction of mosquito repellents for clothing application
No full textInternational audienceUse of protective clothing is a simple and efficient way to reduce the contacts with mosquitoes and consequently the probability of transmission of diseases spread by them. This mechanical barrier can be enhanced by the application of repellents. Unfortunately the number of available repellents is limited. As a result, there is a crucial need to find new active and safer molecules repelling mosquitoes. In this context, a structure-activity relationship (SAR) model was proposed for the design of repellents active on clothing. It was computed from a dataset of 2027 chemicals for which repellent activity on clothing was measured against Aedes aegypti. Molecules were described by means of 20 molecular descriptors encoding physicochemical properties, topological information and structural features. A three-layer perceptron was used as statistical tool. An accuracy of 87% was obtained for both the training and test sets. Most of the wrong predictions can be explained. Avenues for increasing the performances of the model have been proposed
